The present invention relates to wortmannin analogs, and methods of using these derivatives alone or in combination with chemotherapeutic agents to inhibit PI-3-kinase activity and to treat certain malignant tumors and other cancers. Wortmannin is a known potent inhibitor of phosphotidylinositol-3-kinase (PI-3-kinase) and anti-cancer agent. Wortmannin is a naturally occurring compound isolated from culture broths of the fungus Penicillium wortmannin and has the basic structure shown in U.S. Pat. No. 5,480,906, which is incorporated herein by reference.